Regulatory networks defining EMT during cancer initiation and progression

Nature Reviews Cancer

Volumn 13, Issue 2, 2013, Pages 97-110

  Craene, Bram De ^a,b   Berx, Geert ^a,b  

^a GHENT UNIVERSITY   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

BMI1 PROTEIN; GOOSECOID PROTEIN; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE H3; HISTONE METHYLTRANSFERASE; LYSINE SPECIFIC DEMETHYLASE 1; LYSYL OXIDASE LIKE 2 PROTEIN; MICRORNA; POLYCOMB GROUP PROTEIN; PROTEIN; SIRTUIN 1; SUPPRESSOR OF ZESTE 12 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR BRACHYURY; TRANSCRIPTION FACTOR E2 2; TRANSCRIPTION FACTOR E47; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR FOXC2; TRANSCRIPTION FACTOR KLF8; TRANSCRIPTION FACTOR PRRX1; TRANSCRIPTION FACTOR SIX1; TRANSCRIPTION FACTOR SNAI1; TRANSCRIPTION FACTOR SNAI2; TRANSCRIPTION FACTOR TWIST1; TRANSCRIPTION FACTOR ZEB1; TRANSCRIPTION FACTOR ZEB2; UNCLASSIFIED DRUG; UNTRANSLATED RNA; UVOMORULIN;

ALTERNATIVE RNA SPLICING; BASEMENT MEMBRANE; CANCER CELL; CANCER GROWTH; CANCER RECURRENCE; CANCER STEM CELL; CANCER THERAPY; CARCINOGENESIS; CELL SURVIVAL; DEAMINATION; EPITHELIAL MESENCHYMAL TRANSITION; EXON SKIPPING; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; HISTONE METHYLATION; HOMEOSTASIS; HUMAN; METASTASIS; NONHUMAN; PHENOTYPIC PLASTICITY; PRIORITY JOURNAL; PROTEIN STABILITY; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; DISEASE PROGRESSION; EPITHELIAL CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; NEOPLASMS;

EID: 84873050284     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc3447     Document Type: Review

References (270)

1. Nieto, M. A. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu. Rev. Cell Dev. Biol. 27, 347-376 (2011
2. Savagner, P., Yamada, K. M. & Thiery, J. P. The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J. Cell Biol. 137, 1403-1419 (1997
3. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442-454 (2002
4. Batlle, E. et al.The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biol. 2, 84-89 (2000
5. Cano, A. et al.The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biol. 2, 76-83 (2000
6. Nieto, M. A. & Cano, A. The epithelial-mesenchymal transition under control: Global programs to regulate epithelial plasticity. Semin. Cancer Biol. 22, 361-368 (2012
7. De Craene, B., van Roy, F. & Berx, G. Unraveling signalling cascades for the Snail family of transcription factors. Cell Signal 17, 535-547 (2005
8. Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890 (2009
9. Ansieau, S. et al.Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell 14, 79-89 (2008
10. Mejlvang, J. et al.Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Mol. Biol. Cell 18, 4615-4624 (2007
11. Sanchez-Martin, M. et al.Deletion of the SLUG (SNAI2) gene results in human piebaldism. Am. J. Med. Genet. A 122A, 125-132 (2003
12. Perez-Losada, J. et al.Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway. Blood 100, 1274-1286 (2002
13. Horvay, K., Casagranda, F., Gany, A., Hime, G. R. & Abud, H. E. Wnt signaling regulates Snai1 expression and cellular localization in the mouse intestinal epithelial stem cell niche. Stem Cells Dev. 20, 737-745 (2011
14. Foubert, E., De Craene, B. & Berx, G. Key signalling nodes in mammary gland development and cancer. The Snail1-Twist1 conspiracy in malignant breast cancer progression. Breast Cancer Res. 12, 206 (2010
15. Lee, K., Gjorevski, N., Boghaert, E., Radisky, D. C. & Nelson, C. M. Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis. EMBO J. 30, 2662-2674 (2011
16. Brabletz, T. To differentiate or not - routes towards metastasis. Nature Rev. Cancer 12, 425-436 (2012
17. Li, R. et al.A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7, 51-63 (2010
18. Samavarchi-Tehrani, P. et al.Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 7, 64-77 (2010
19. Goossens, S. et al.The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/ progenitor cell differentiation and mobilization. Blood 117, 5620-5630 (2011
20. Postigo, A. A. & Dean, D. C. Independent repressor domains in ZEB regulate muscle and T-cell differentiation. Mol. Cell. Biol. 19, 7961-7971 (1999
21. Yang, D. J. et al.Slug, mammalian homologue gene of Drosophila escargot, promotes neuronal-differentiation through suppression of HEB/ daughterless. Cell Cycle 9, 2789-2802 (2010
22. Boutet, A. et al.Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J. 25, 5603-5613 (2006
23. Perez-Mancera, P. A. et al.Cancer development induced by graded expression of Snail in mice. Hum. Mol. Genet. 14, 3449-3461 (2005
24. Morel, A. P. et al.EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. PLoS Genet. 8, e1002723 (2012
25. Rhim, A. D. et al.EMT and dissemination precede pancreatic tumor formation. Cell 148, 349-361 (2012
26. Hajra, K. M., Chen, D. Y. & Fearon, E. R. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res. 62, 1613-1618 (2002
27. Comijn, J. et al.The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol. Cell 7, 1267-1278 (2001
28. Eger, A. et al.DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 24, 2375-2385 (2005
29. Perez-Moreno, M. A. et al.A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J. Biol. Chem. 276, 27424-27431 (2001
30. Wang, X. et al.Krüppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Res. 67, 7184-7193 (2007
31. Fernando, R. I. et al.The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J. Clin. Invest. 120, 533-544 (2010
32. De Craene, B. et al.The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program. Cancer Res. 65, 6237-6244 (2005
33. Moreno-Bueno, G. et al.Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition. Cancer Res. 66, 9543-9556 (2006
34. Vandewalle, C. et al.SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res. 33, 6566-6578 (2005
35. Yang, J. et al.Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927-939 (2004
36. Mani, S. A. et al.Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc. Natl Acad. Sci. USA 104, 10069-10074 (2007
37. Hartwell, K. A. et al.The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc. Natl Acad. Sci. USA 103, 18969-18974 (2006
38. Sobrado, V. R. et al.The class I bHLH factors E2-2A and E2-2B regulate EMT. J. Cell Sci. 122, 1014-1024 (2009
39. McCoy, E. L. et al.Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial- mesenchymal transition. J. Clin. Invest. 119, 2663-2677 (2009
40. Ocana, O. H. et al.Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 699-701 (2012
41. Frisch, S. M. The epithelial cell default-phenotype hypothesis and its implications for cancer. Bioessays 19, 705-709 (1997
42. Chakrabarti, R. et al.Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biol. 14, 1212-1222 (2012
43. Cieply, B. et al.Suppression of the epithelial- mesenchymal transition by Grainyhead-like-2. Cancer Res. 72, 2440-2453 (2012
44. Graff, J. R., Gabrielson, E., Fujii, H., Baylin, S. B. & Herman, J. G. Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J. Biol. Chem. 275, 2727-2732 (2000
45. Lombaerts, M. et al.E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br. J. Cancer 94, 661-671 (2006
46. Cheng, C. W. et al.Mechanisms of inactivation of E-cadherin in breast carcinoma: Modification of the two-hit hypothesis of tumor suppressor gene. Oncogene 20, 3814-3823 (2001
47. Espada, J. et al.Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context. Nucleic Acids Res. 39, 9194-9205 (2011
48. Rodriguez-Paredes, M. & Esteller, M. Cancer epigenetics reaches mainstream oncology. Nature Med. 17, 330-339 (2011
49. Peinado, H., Ballestar, E., Esteller, M. & Cano, A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol. Cell. Biol. 24, 306-319 (2004
50. Byles, V. et al.SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene 31, 4619-4629 (2012
51. Lin, T., Ponn, A., Hu, X., Law, B. K. & Lu, J. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene 29, 4896-4904 (2010
52. Herranz, N. et al.Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol. Cell. Biol. 28, 4772-4781 (2008
53. Dong, C. et al.Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer. Oncogene 7 May 2012 (doi:10.1038/ onc.2012.169
54. Dong, C. et al.G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J. Clin. Invest. 122, 1469-1486 (2012
55. Sanchez-Tillo, E. et al.ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene 29, 3490-3500 (2010
56. Yang, M. H. et al.Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nature Cell Biol. 12, 982-992 (2010
57. Peinado, H. et al.A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. EMBO J. 24, 3446-3458 (2005
58. Herranz, N. et al.Lysyl oxidase-like 2 deaminates lysine 4 in histone H3. Mol. Cell 46, 369-376 (2012
59. Wu, M. Z. et al.Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition. Mol. Cell 43, 811-822 (2011
60. McDonald, O. G., Wu, H., Timp, W., Doi, A. & Feinberg, A. P. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition. Nature Struct. Mol. Biol. 18, 867-874 (2011
61. Ke, X. S. et al.Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells. BMC Genomics 11, 669 (2010
62. Hugo, H. J. et al.Defining the E-cadherin repressor interactome in epithelial-mesenchymal transition: The PMC42 model as a case study. Cells Tissues Organs 193, 23-40 (2011
63. Taube, J. H. et al.Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc. Natl Acad. Sci. USA 107, 15449-15454 (2010
64. Casas, E. et al.Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 71, 245-254 (2011
65. Olmeda, D. et al.Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines. Oncogene 27, 4690-4701 (2008
66. Spaderna, S. et al.The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68, 537-544 (2008
67. Vega, S. et al.Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 18, 1131-1143 (2004
68. Mani, S. A. et al.The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704-715 (2008
69. Wellner, U. et al.The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nature Cell Biol. 11, 1487-1495 (2009
70. Zhang, J. & Ma, L. MicroRNA control of epithelial- mesenchymal transition and metastasis. Cancer Metastasis Rev. 31, 653-662 (2012
71. Gregory, P. A. et al.The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol. 10, 593-601 (2008
72. Park, S. M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22, 894-907 (2008
73. Korpal, M., Lee, E. S., Hu, G. & Kang, Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem. 283, 14910-14914 (2008
74. Iliopoulos, D. et al.Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol. Cell 39, 761-772 (2012
75. Kim, N. H. et al.A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J. Cell Biol. 195, 417-433 (2011
76. Siemens, H. et al.miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 10, 4256-4271 (2011
77. Burk, U. et al.A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 9, 582-589 (2008
78. Varambally, S. et al.Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695-1699 (2008
79. Shimono, Y. et al.Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138, 592-603 (2009
80. Greene, S. B., Gunaratne, P. H., Hammond, S. M. & Rosen, J. M. A putative role for microRNA-205 in mammary epithelial cell progenitors. J. Cell Sci. 123, 606-618 (2010
81. Kong, D. et al.Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS ONE 5, e12445 (2010
82. Chang, C. J. et al.p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nature Cell Biol. 13, 317-323 (2011
83. Choi, Y. J. et al.miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nature Cell Biol. 13, 1353-1360 (2011
84. Kim, T. et al.p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J. Exp. Med. 208, 875-883 (2011
85. Bonizzi, G., Cicalese, A., Insinga, A. & Pelicci, P. G. The emerging role of p53 in stem cells. Trends Mol. Med. 18, 6-12 (2012
86. Dong, P. et al.Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene 30 Jul 2012 (doi:10.1038/onc.2012.334
87. Adorno, M. et al.A mutant-p53/Smad complex opposes p63 to empower TGFβ-induced metastasis. Cell 137, 87-98 (2009
88. Vrba, L. et al.Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS ONE 5, e8697 (2010
89. Bhatnagar, N. et al.Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis. 1, e105 (2010
90. Tellez, C. S. et al.EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells. Cancer Res. 71, 3087-3097 (2011
91. Davalos, V. et al.Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene 31, 2062-2074 (2012
92. Hur, K. et al.MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 26 Jun 2012 (doi:10.1136/ gutjnl-2011-301846
93. Korpal, M. et al.Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Med. 17, 1101-1108 (2011
94. Ma, L. et al.miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biol. 12, 247-256 (2010
95. Chen, Z. L. et al.microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J. Biol. Chem. 286, 10725-10734 (2011
96. Turcatel, G., Rubin, N., El-Hashash, A. & Warburton, D. MIR-99a and MIR-99b modulate TGF-β induced epithelial to mesenchymal plasticity in normal murine mammary gland cells. PLoS ONE 7, e31032 (2012
97. Beltran, M. et al.A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 22, 756-769 (2008
98. Karreth, F. A. et al.In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147, 382-395 (2011
99. Ghigna, C. et al.Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol. Cell 20, 881-890 (2005
100. Savagner, P., Valles, A. M., Jouanneau, J., Yamada, K. M. & Thiery, J. P. Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial- mesenchymal transition in rat bladder carcinoma cells. Mol. Biol. Cell 5, 851-862 (1994
101. Valacca, C. et al.Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J. Cell Biol. 191, 87-99 (2010
102. Warzecha, C. C., Sato, T. K., Nabet, B., Hogenesch, J. B. & Carstens, R. P. ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Mol. Cell 33, 591-601 (2009
103. Yanagisawa, M. et al.A p120 catenin isoform switch affects Rho activity, induces tumor cell invasion, and predicts metastatic disease. J. Biol. Chem. 283, 18344-18354 (2008
104. Warzecha, C. C. et al.An ESRP-regulated splicing programme is abrogated during the epithelial- mesenchymal transition. EMBO J. 29, 3286-3300 (2010
105. Hartwell, K. A. et al.The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc. Natl Acad. Sci. USA 103, 18969-18974 (2006
106. Sobrado, V. R. et al.The class I bHLH factors E2-2A and E2-2B regulate EMT. J. Cell Sci. 122, 1014-1024 (2009
107. McCoy, E. L. et al.Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial- mesenchymal transition. J. Clin. Invest. 119, 2663-2677 (2009
108. Ocana, O. H. et al.Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 699-701 (2012
109. Frisch, S. M. The epithelial cell default-phenotype hypothesis and its implications for cancer. Bioessays 19, 705-709 (1997
110. Chakrabarti, R. et al.Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biol. 14, 1212-1222 (2012
111. Cieply, B. et al.Suppression of the epithelial- mesenchymal transition by Grainyhead-like-2. Cancer Res. 72, 2440-2453 (2012
112. Graff, J. R., Gabrielson, E., Fujii, H., Baylin, S. B. & Herman, J. G. Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J. Biol. Chem. 275, 2727-2732 (2000
113. Lombaerts, M. et al.E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br. J. Cancer 94, 661-671 (2006
114. Cheng, C. W. et al.Mechanisms of inactivation of E-cadherin in breast carcinoma: Modification of the two-hit hypothesis of tumor suppressor gene. Oncogene 20, 3814-3823 (2001
115. Espada, J. et al.Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context. Nucleic Acids Res. 39, 9194-9205 (2011
116. Rodriguez-Paredes, M. & Esteller, M. Cancer epigenetics reaches mainstream oncology. Nature Med. 17, 330-339 (2011
117. Peinado, H., Ballestar, E., Esteller, M. & Cano, A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol. Cell. Biol. 24, 306-319 (2004
118. Byles, V. et al.SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene 31, 4619-4629 (2012
119. Lin, T., Ponn, A., Hu, X., Law, B. K. & Lu, J. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene 29, 4896-4904 (2010
120. Herranz, N. et al.Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol. Cell. Biol. 28, 4772-4781 (2008
121. Dong, C. et al.Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer. Oncogene 7 May 2012 (doi:10.1038/ onc.2012.169
122. Dong, C. et al.G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J. Clin. Invest. 122, 1469-1486 (2012
123. Sanchez-Tillo, E. et al.ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene 29, 3490-3500 (2010
124. Yang, M. H. et al.Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nature Cell Biol. 12, 982-992 (2010
125. Peinado, H. et al.A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. EMBO J. 24, 3446-3458 (2005
126. Herranz, N. et al.Lysyl oxidase-like 2 deaminates lysine 4 in histone H3. Mol. Cell 46, 369-376 (2012
127. Wu, M. Z. et al.Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition. Mol. Cell 43, 811-822 (2011
128. McDonald, O. G., Wu, H., Timp, W., Doi, A. & Feinberg, A. P. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition. Nature Struct. Mol. Biol. 18, 867-874 (2011
129. Ke, X. S. et al.Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells. BMC Genomics 11, 669 (2010
130. Hugo, H. J. et al.Defining the E-cadherin repressor interactome in epithelial-mesenchymal transition: The PMC42 model as a case study. Cells Tissues Organs 193, 23-40 (2011
131. Taube, J. H. et al.Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc. Natl Acad. Sci. USA 107, 15449-15454 (2010
132. Casas, E. et al.Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 71, 245-254 (2011
133. Olmeda, D. et al.Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines. Oncogene 27, 4690-4701 (2008
134. Spaderna, S. et al.The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68, 537-544 (2008
135. Vega, S. et al.Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 18, 1131-1143 (2004
136. Mani, S. A. et al.The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133, 704-715 (2008
137. Wellner, U. et al.The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nature Cell Biol. 11, 1487-1495 (2009
138. Zhang, J. & Ma, L. MicroRNA control of epithelial- mesenchymal transition and metastasis. Cancer Metastasis Rev. 31, 653-662 (2012
139. Gregory, P. A. et al.The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol. 10, 593-601 (2008
140. Park, S. M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22, 894-907 (2008
141. Korpal, M., Lee, E. S., Hu, G. & Kang, Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem. 283, 14910-14914 (2008
142. Iliopoulos, D. et al.Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol. Cell 39, 761-772 (2012
143. Kim, N. H. et al.A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J. Cell Biol. 195, 417-433 (2011
144. Siemens, H. et al.miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 10, 4256-4271 (2011
145. Burk, U. et al.A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 9, 582-589 (2008
146. Varambally, S. et al.Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695-1699 (2008
147. Shimono, Y. et al.Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138, 592-603 (2009
148. Greene, S. B., Gunaratne, P. H., Hammond, S. M. & Rosen, J. M. A putative role for microRNA-205 in mammary epithelial cell progenitors. J. Cell Sci. 123, 606-618 (2010
149. Kong, D. et al.Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS ONE 5, e12445 (2010
150. Chang, C. J. et al.p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nature Cell Biol. 13, 317-323 (2011
151. Choi, Y. J. et al.miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nature Cell Biol. 13, 1353-1360 (2011
152. Kim, T. et al.p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J. Exp. Med. 208, 875-883 (2011
153. Bonizzi, G., Cicalese, A., Insinga, A. & Pelicci, P. G. The emerging role of p53 in stem cells. Trends Mol. Med. 18, 6-12 (2012
154. Dong, P. et al.Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene 30 Jul 2012 (doi:10.1038/onc.2012.334
155. Adorno, M. et al.A mutant-p53/Smad complex opposes p63 to empower TGFβ-induced metastasis. Cell 137, 87-98 (2009
156. Vrba, L. et al.Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS ONE 5, e8697 (2010
157. Bhatnagar, N. et al.Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis. 1, e105 (2010
158. Tellez, C. S. et al.EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells. Cancer Res. 71, 3087-3097 (2011
159. Davalos, V. et al.Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene 31, 2062-2074 (2012
160. Hur, K. et al.MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 26 Jun 2012 (doi:10.1136/ gutjnl-2011-301846
161. Korpal, M. et al.Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Med. 17, 1101-1108 (2011
162. Ma, L. et al.miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biol. 12, 247-256 (2010
163. Chen, Z. L. et al.microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J. Biol. Chem. 286, 10725-10734 (2011
164. Turcatel, G., Rubin, N., El-Hashash, A. & Warburton, D. MIR-99a and MIR-99b modulate TGF-β induced epithelial to mesenchymal plasticity in normal murine mammary gland cells. PLoS ONE 7, e31032 (2012
165. Beltran, M. et al.A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 22, 756-769 (2008
166. Karreth, F. A. et al.In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147, 382-395 (2011
167. Ghigna, C. et al.Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol. Cell 20, 881-890 (2005
168. Savagner, P., Valles, A. M., Jouanneau, J., Yamada, K. M. & Thiery, J. P. Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial- mesenchymal transition in rat bladder carcinoma cells. Mol. Biol. Cell 5, 851-862 (1994
169. Valacca, C. et al.Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J. Cell Biol. 191, 87-99 (2010
170. Warzecha, C. C., Sato, T. K., Nabet, B., Hogenesch, J. B. & Carstens, R. P. ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Mol. Cell 33, 591-601 (2009
171. Yanagisawa, M. et al.A p120 catenin isoform switch affects Rho activity, induces tumor cell invasion, and predicts metastatic disease. J. Biol. Chem. 283, 18344-18354 (2008
172. Warzecha, C. C. et al.An ESRP-regulated splicing programme is abrogated during the epithelial- mesenchymal transition. EMBO J. 29, 3286-3300 (2010
173. Horiguchi, K. et al.TGF-β drives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP. Oncogene 31, 3190-3201 (2012
174. Reinke, L. M., Xu, Y. & Cheng, C. Snail represses the splicing regulator epithelial splicing regulatory protein 1 to promote epithelial-mesenchymal transition. J. Biol. Chem. 287, 36435-36442 (2012
175. Shapiro, I. M. et al.An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 7, e1002218 (2011
176. Lapuk, A. et al.Exon-level microarray analyses identify alternative splicing programs in breast cancer. Mol. Cancer Res. 8, 961-974 (2010
177. Evdokimova, V. et al.Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell 15, 402-415 (2009
178. Hussey, G. S. et al.Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Mol. Cell 41, 419-431 (2011
179. Bachelder, R. E., Yoon, S. O., Franci, C., de Herreros, A. G. & Mercurio, A. M. Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: Implications for the epithelial- mesenchymal transition. J. Cell Biol. 168, 29-33 (2005
180. Xu, Y. et al.Role of CK1 in GSK3β-mediated phosphorylation and degradation of snail. Oncogene 29, 3124-3133 (2010
181. Yook, J. I., Li, X. Y., Ota, I., Fearon, E. R. & Weiss, S. J. Wnt-dependent regulation of the E-cadherin repressor snail. J. Biol. Chem. 280, 11740-11748 (2005
182. Zhou, B. P. et al.Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nature Cell Biol. 6, 931-940 (2004
183. Wu, Y. et al.Stabilization of snail by NF-κB is required for inflammation-induced cell migration and invasion. Cancer Cell 15, 416-428 (2009
184. Wu, Z. Q. et al.Canonical Wnt signaling regulates Slug activity and links epithelial-mesenchymal transition with epigenetic breast cancer 1, early onset (BRCA1) repression. Proc. Natl Acad. Sci. USA 109, 16654-16659 (2012
185. Vinas-Castells, R. et al.The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation. J. Biol. Chem. 285, 3794-3805 (2010
186. Lim, S. O. et al.Notch1 binds and induces degradation of Snail in hepatocellular carcinoma. BMC Biol. 9, 83 (2011
187. Wang, S. P. et al.p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nature Cell Biol. 11, 694-704 (2009
188. Lander, R., Nordin, K. & LaBonne, C. The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1. J. Cell Biol. 194, 17-25 (2011
189. Sun, M. et al.Activation of the ATM-Snail pathway promotes breast cancer metastasis. J. Mol. Cell. Biol. 4, 304-315 (2012
190. Yang, Z. et al.Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions. Cancer Res. 65, 3179-3184 (2005
191. Park, S. Y. et al.Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J. 29, 3787-3796 (2010
192. Radisky, D. C. et al.Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436, 123-127 (2005
193. Jung, H. et al.TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition. Oncogene 27, 2635-2647 (2008
194. Billottet, C. et al.Modulation of several waves of gene expression during FGF-1 induced epithelial- mesenchymal transition of carcinoma cells. J. Cell. Biochem. 104, 826-839 (2008
195. Eckert, M. A. et al.Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell 19, 372-386 (2011
196. Gligorijevic, B. et al.N-WASP-mediated invadopodium formation is involved in intravasation and lung metastasis of mammary tumors. J. Cell Sci. 125, 724-734 (2012
197. Wyckoff, J. B. et al.Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 67, 2649-2656 (2007
198. Zhang, K. et al.Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. EMBO J. 31, 29-43 (2012
199. Yamashita, S. et al.Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature 429, 298-302 (2004
200. Lei, Q. Y. et al.TAZ promotes cell proliferation and epithelial-
201. Cordenonsi, M. et al.The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147, 759-772 (2011
202. Varelas, X. et al.The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. Dev. Cell 19, 831-844 (2010
203. Du, C., Zhang, C., Hassan, S., Biswas, M. H. & Balaji, K. C. Protein kinase D1 suppresses epithelial-to-mesenchymal transition through phosphorylation of snail. Cancer Res. 70, 7810-7819 (2010
204. Gheldof, A., Hulpiau, P., van Roy, F., De Craene, B. & Berx, G. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell. Mol. Life Sci. 69, 2527-2541 (2012
205. Inuzuka, T., Tsuda, M., Kawaguchi, H. & Ohba, Y. Transcription factor 8 activates R-Ras to regulate angiogenesis. Biochem. Biophys. Res. Commun. 379, 510-513 (2009
206. Long, J., Zuo, D. & Park, M. Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin. J. Biol. Chem. 280, 35477-35489 (2005
207. Brabletz, T., Jung, A., Spaderna, S., Hlubek, F. & Kirchner, T. Opinion: Migrating cancer stem cells - an integrated concept of malignant tumour progression. Nature Rev. Cancer 5, 744-749 (2005
208. Berx, G. & van Roy, F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harbor Persp. Biol. 1, a003129 (2009
209. Sarrio, D. et al.Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 68, 989-997 (2008
210. Hennessy, B. T. et al.Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 69, 4116-4124 (2009
211. Herschkowitz, J. I. et al.Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 8, R76 (2007
212. Gradilone, A. et al.Circulating tumour cells lacking cytokeratin in breast cancer: The importance of being mesenchymal. J. Cell. Mol. Med. 15, 1066-1070 (2011
213. Trimboli, A. J. et al.Direct evidence for epithelial- mesenchymal transitions in breast cancer. Cancer Res. 68, 937-945 (2008
214. Becker, K. F. et al.Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs 185, 204-212 (2007
215. Sanchez-Tillo, E. et al.EMT-activating transcription factors in cancer: Beyond EMT and tumor invasiveness. Cell. Mol. Life Sci. 69, 3429-3456 (2012
216. Alves, C. C., Carneiro, F., Hoefler, H. & Becker, K. F. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front. Biosci. 14, 3035-3050 (2009
217. Castro Alves, C. et al.Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J. Pathol. 211, 507-515 (2007
218. Patel, D. & Chaudhary, J. Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis. Biochem. Biophys. Res. Commun. 422, 146-151 (2012
219. Lahiri, S. K. & Zhao, J. Krüppel-like factor 8 emerges as an important regulator of cancer. Am. J. Transl. Res. 4, 357-363 (2012
220. Kilic, N. et al.Brachyury expression predicts poor prognosis at early stages of colorectal cancer. Eur. J. Cancer 47, 1080-1085 (2011
221. Roselli, M. et al.Brachyury, a driver of the epithelial- mesenchymal transition, is overexpressed in human lung tumors: An opportunity for novel interventions against lung cancer. Clin. Cancer Res. 18, 3868-3879 (2012
222. Jiang, W. et al.Prognostic role of Twist, Slug, and Foxc2 expression in stage I non-small-cell lung cancer after curative resection. Clin. Lung Cancer 13, 280-287 (2012
223. Nishida, N. et al.FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma. Ann. Surg. Oncol. 18, 535-542 (2011
224. Watanabe, T. et al.Gene expression of mesenchyme forkhead 1 (FOXC2) significantly correlates with the degree of lymph node metastasis in colorectal cancer. Int. Surg. 96, 207-216 (2011
225. Cano, A. & Portillo, F. An emerging role for class I bHLH E2-2 proteins in EMT regulation and tumor progression. Cell Adh. Migr. 4, 56-60 (2010
226. Iwanaga, R. et al.Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-β signaling pathways. Breast Cancer Res. 14, R100 (2012
227. Qamar, L. et al.Specificity and prognostic validation of a polyclonal antibody to detect Six1 homeoprotein in ovarian cancer. Gynecol. Oncol. 125, 451-457 (2012
228. Tan, J., Zhang, C. & Qian, J. Expression and significance of Six1 and Ezrin in cervical cancer tissue. Tumour Biol. 32, 1241-1247 (2011
229. Barneda-Zahonero, B. & Parra, M. Histone deacetylases and cancer. Mol. Oncol. 6, 579-589 (2012
230. Liu, T., Liu, P. Y. & Marshall, G. M. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 69, 1702-1705 (2009
231. Sauvageau, M. & Sauvageau, G. Polycomb group proteins: Multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell 7, 299-313 (2010
232. Bennani-Baiti, I. M., Machado, I., Llombart-Bosch, A. & Kovar, H. Lysine-specific demethylase 1 (LSD1/ KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Hum. Pathol. 43, 1300-1307 (2012
233. Hayami, S. et al.Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int. J. Cancer 128, 574-586 (2011
234. Kahl, P. et al.Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 66, 11341-11347 (2006
235. Kauffman, E. C. et al.Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol. Carcinog. 50, 931-944 (2011
236. Lim, S. et al.Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 31, 512-520 (2010
237. Lv, T. et al.Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS ONE 7, e35065 (2012
238. Kang, M. Y. et al.Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer. Int. J. Cancer 121, 2192-2197 (2007
239. Chen, M. W. et al.H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res. 70, 7830-7840 (2010
240. Barker, H. E., Cox, T. R. & Erler, J. T. The rationale for targeting the LOX family in cancer. Nature Rev. Cancer 12, 540-552 (2012
241. Cano, A., Santamaria, P. G. & Moreno-Bueno, G. LOXL2 in epithelial cell plasticity and tumor progression. Future Oncol. 8, 1095-1108 (2012
242. Nishioka, T., Eustace, A. & West, C. Lysyl oxidase: From basic science to future cancer treatment. Cell Struct. Funct. 37, 75-80 (2012
243. Hu, X. et al.A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol. Oncol. 114, 457-464 (2009
244. Shinozaki, A. et al.Downregulation of microRNA-200 in EBV-associated gastric carcinoma. Cancer Res. 70, 4719-4727 (2010
245. Wiklund, E. D. et al.Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int. J. Cancer 128, 1327-1334 (2011
246. Zidar, N. et al.Down-regulation of microRNAs of the miR-200 family and miR-205, and an altered expression of classic and desmosomal cadherins in spindle cell carcinoma of the head and neck-hallmark of epithelial-mesenchymal transition. Hum. Pathol. 42, 482-488 (2011
247. Gravgaard, K. H. et al.The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer. Breast Cancer Res. Treat. 134, 207-217 (2012
248. Karaayvaz, M., Zhang, C., Liang, S., Shroyer, K. R. & Ju, J. Prognostic significance of miR-205 in endometrial cancer. PLoS ONE 7, e35158 (2012
249. Lee, J. W. et al.The expression of the miRNA-200 family in endometrial endometrioid carcinoma. Gynecol. Oncol. 120, 56-62 (2011
250. Li, A. et al.Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer Res. 70, 5226-5237 (2010
251. Snowdon, J., Zhang, X., Childs, T., Tron, V. A. & Feilotter, H. The microRNA-200 family is upregulated in endometrial carcinoma. PLoS ONE 6, e22828 (2011
252. Valladares-Ayerbes, M. et al.Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer. J. Transl. Med. 10, 186 (2012
253. Boll, K. et al.MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene 5 Mar 2012 (doi:10.1038/onc.2012.55
254. Childs, G. et al.Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am. J. Pathol. 174, 736-745 (2009
255. Hanna, J. A., Hahn, L., Agarwal, S. & Rimm, D. L. In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA. Lab. Invest. 92, 1390-1397 (2012
256. Philippidou, D. et al.Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res. 70, 4163-4173 (2010
257. Xu, Y., Brenn, T., Brown, E. R., Doherty, V. & Melton, D. W. Differential expression of microRNAs during melanoma progression: MiR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br. J. Cancer 106, 553-561 (2012
258. Markou, A. et al.Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin. Chem. 54, 1696-1704 (2008
259. Corney, D. C. et al.Frequent downregulation of miR-34 family in human ovarian cancers. Clin. Cancer Res. 16, 1119-1128 (2010
260. Vogt, M. et al.Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 458, 313-322 (2011
261. Wang, Z. et al.DNA hypermethylation of microRNA-34b/c has prognostic value for stage non-small cell lung cancer. Cancer Biol. Ther. 11, 490-496 (2011
262. Carvalho, J. et al.Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. J. Pathol. 228, 31-44 (2012
263. Luo, L. et al.MiR-101 and Mcl-1 in non-small-cell lung cancer: Expression profile and clinical significance. Med. Oncol. 29, 1681-1686 (2012
264. Su, H. et al.MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 69, 1135-1142 (2009
265. Wang, H. J. et al.MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur. J. Cancer 46, 2295-2303 (2010
266. Yuva-Aydemir, Y., Simkin, A., Gascon, E. & Gao, F. B. MicroRNA-9: Functional evolution of a conserved small regulatory RNA. RNA Biol. 8, 557-564 (2011
267. Chaudhury, A. et al.TGF-β-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nature Cell Biol. 12, 286-293 (2010
268. Ong, C. C. et al.Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells. Proc. Natl Acad. Sci. USA 108, 7177-7182 (2011
269. Li, L. H. et al.P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis. Oncol. Rep. 27, 1435-1442 (2012
270. Taylor, K. M. & Nicholson, R. I. The LZT proteins; the LIV-1 subfamily of zinc transporters. Biochim. Biophys. Acta 1611, 16-30 (2003